Albillos Agustín, Zamora Javier, Martínez Javier, Arroyo David, Ahmad Irfan, De-la-Peña Joaquin, Garcia-Pagán Juan-Carlos, Lo Gin-Ho, Sarin Shiv, Sharma Barjesh, Abraldes Juan G, Bosch Jaime, Garcia-Tsao Guadalupe
Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, University of Alcalá, IRYCIS, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.
Hepatology. 2017 Oct;66(4):1219-1231. doi: 10.1002/hep.29267. Epub 2017 Aug 26.
Endoscopic variceal ligation plus beta-blockers (EVL+BB) is currently recommended for variceal rebleeding prophylaxis, a recommendation that extends to all patients with cirrhosis with previous variceal bleeding irrespective of prognostic stage. Individualizing patient care is relevant, and in published studies on variceal rebleeding prophylaxis, there is a lack of information regarding response to therapy by prognostic stage. This study aimed at comparing EVL plus BB with monotherapy (EVL or BB) on all-source rebleeding and mortality in patients with cirrhosis and previous variceal bleeding stratified by cirrhosis severity (Child A versus B/C) by means of individual time-to-event patient data meta-analysis from randomized controlled trials. The study used individual data on 389 patients from three trials comparing EVL plus BB versus BB and 416 patients from four trials comparing EVL plus BB versus EVL. Compared with BB alone, EVL plus BB reduced overall rebleeding in Child A (incidence rate ratio 0.40; 95% confidence interval, 0.18-0.89; P = 0.025) but not in Child B/C, without differences in mortality. The effect of EVL on rebleeding was different according to Child (P for interaction <0.001). Conversely, compared with EVL, EVL plus BB reduced rebleeding in both Child A and B/C, with a significant reduction in mortality in Child B/C (incidence rate ratio 0.46; 95% confidence interval, 0.25-0.85; P = 0.013).
Outcomes of therapies to prevent variceal rebleeding differ depending on cirrhosis severity: in patients with preserved liver function (Child A), combination therapy is recommended because it is more effective in preventing rebleeding, without modifying survival, while in patients with advanced liver failure (Child B/C), EVL alone carries an increased risk of rebleeding and death compared with combination therapy, underlining that BB is the key element of combination therapy. (Hepatology 2017;66:1219-1231).
目前推荐内镜下静脉曲张结扎术联合β受体阻滞剂(EVL+BB)用于预防静脉曲张再出血,这一推荐适用于所有既往有静脉曲张出血的肝硬化患者,无论其预后分期如何。个体化的患者护理很重要,而在已发表的关于预防静脉曲张再出血的研究中,缺乏按预后分期对治疗反应的相关信息。本研究旨在通过对随机对照试验中个体事件发生时间的患者数据进行荟萃分析,比较EVL联合BB与单一疗法(EVL或BB)对肝硬化且既往有静脉曲张出血患者按肝硬化严重程度(Child A与B/C)分层后的全因再出血和死亡率的影响。该研究使用了来自三项比较EVL联合BB与BB的试验中的389例患者的个体数据,以及来自四项比较EVL联合BB与EVL的试验中的416例患者的个体数据。与单独使用BB相比,EVL联合BB降低了Child A患者的总体再出血率(发生率比值0.40;95%置信区间,0.18 - 0.89;P = 0.025),但在Child B/C患者中未降低,死亡率无差异。EVL对再出血的影响因Child分级而异(交互作用P<0.001)。相反,与EVL相比,EVL联合BB降低了Child A和B/C患者的再出血率,Child B/C患者的死亡率显著降低(发生率比值0.46;95%置信区间,0.25 - 0.85;P = 0.013)。
预防静脉曲张再出血的治疗结果因肝硬化严重程度而异:在肝功能保留的患者(Child A)中,推荐联合治疗,因为它在预防再出血方面更有效,且不影响生存率,而在晚期肝衰竭患者(Child B/C)中,与联合治疗相比,单独使用EVL再出血和死亡风险增加,这突出了BB是联合治疗的关键要素。(《肝脏病学》2017年;66:1219 - 1231)